Class 1, 2, and 3 BRAF-mutated metastatic colorectal cancer: A detailed clinical, pathologic, and molecular characterization
| Autor: | Armando Orlandi, Nicoletta Pella, Giada Munari, Claudia Mescoli, Vittorina Zagonel, Umberto Malapelle, Maurizio Martini, Fotios Loupakis, Stefano Cascinu, Francesca Bergamo, Federica Urbano, Giovanna De Maglio, Marta Schirripa, Sara Lonardi, Salvatore Corallo, Massimo Rugge, Paola Biason, Angelo Paolo Dei Tos, Carlotta Antoniotti, Luca Reggiani Bonetti, Chiara Cremolini, Fabio Gelsomino, Gabriella Fontanini, Matteo Fassan, Maria Simona Pino, Giovanni Lanza, Filippo Pietrantonio, Stefano Lazzi, Serena Saggio |
|---|---|
| Přispěvatelé: | Schirripa, M., Biason, P., Lonardi, S., Pella, N., Simona Pino, M., Urbano, F., Antoniotti, C., Cremolini, C., Corallo, S., Pietrantonio, F., Gelsomino, F., Cascinu, S., Orlandi, A., Munari, G., Malapelle, U., Saggio, S., Fontanini, G., Rugge, M., Mescoli, C., Lazzi, S., Bonetti, L. R., Lanza, G., Dei Tos, A. P., De Maglio, G., Martini, M., Bergamo, F., Zagonel, V., Loupakis, F., Fassan, M. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research Colorectal cancer Kaplan-Meier Estimate 0302 clinical medicine BRAF mutation metastatic colorectal cancer CMS CD3/CD8 Cytokeratin personalized medicine 80 and over Lymphocytes Young adult Neoplasm Metastasis Adult Aged Aged 80 and over Biomarkers Tumor Colorectal Neoplasms Female Humans Kaplan-Meier Estimate Lymphocytes Tumor-Infiltrating Male Middle Aged Mutation Neoplasm Grading Neoplasm Metastasis Neoplasm Staging Prognosis Proto-Oncogene Proteins B-raf Young Adult Aged 80 and over Tumor Hazard ratio Middle Aged Prognosis 030220 oncology & carcinogenesis Immunohistochemistry Female Outcome data Colorectal Neoplasms Adult Proto-Oncogene Proteins B-raf medicine.medical_specialty NO 03 medical and health sciences Young Adult Aged Humans Lymphocytes Tumor-Infiltrating Neoplasm Grading Neoplasm Staging Biomarkers Tumor Mutation Internal medicine medicine Tumor-Infiltrating Kinase activity Settore MED/08 - ANATOMIA PATOLOGICA business.industry medicine.disease Confidence interval digestive system diseases 030104 developmental biology business Biomarkers |
| Popis: | Purpose: BRAF mutations are grouped in activating RAS-independent signaling as monomers (class 1–V600E) or as dimers (class 2–codons 597/601), and RAS-dependent with impaired kinase activity (class 3–codons 594/596). Although clinical, pathologic, and molecular features of V600EBRAF-mutated metastatic colorectal cancer (mCRC) are well known, limited data are available from the two other classes. Experimental Design: Data from 117 patients with BRAF (92 class 1, 12 class 2, and 13 class 3)-mutated mCRC were collected. A total of 540 BRAF wt mCRCs were included as control. IHC profiling was performed to determine the consensus molecular subtypes (CMS), cytokeratin 7/20 profiles, tumor-infiltrating lymphocyte infiltration, and BM1/BM2 categorization. Overall survival (OS) and progression-free survival were evaluated by Kaplan–Meier and log-rank test. Results: Class 3 BRAF-mutated mCRC was more frequently left sided (P = 0.0028), pN0 (P = 0.0159), and without peritoneal metastases (P = 0.0176) compared with class 1, whereas class 2 cases were similar to class 1. Hazard ratio for OS, as compared with BRAF wt, was 2.38 [95% confidence interval (CI), 1.61–3.54] for class 1, 1.90 (95% CI, 0.85–4.26) for class 2, and 0.93 (95% CI, 0.51–1.69) for class 3 (P < 0.0001). Class 2 and 3 tumors were all assigned to CMS2-3. A higher median CD3/CD8-positive lymphocyte infiltration was observed in BRAF-mutated class 2 (P = 0.033) compared with class 3 cases. Conclusions: For the first time, different clinical and pathologic features and outcome data were reported according to the three BRAF mutation classes in mCRC. Specific targeted treatment strategies should be identified in the near future for such patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|